Normal aging involves decline across multiple cognitive domains, such as episodic and working memory, thought to reflect subtle changes in brain structure and function. Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by severe episodic memory decline and multiple brain alterations. Interestingly, beta-amyloid plaques, which are the hallmark pathological feature of AD, are commonly found in normal elderly individuals as well, often in amounts comparable to AD. While the impact of beta-amyloid plaques in individuals without dementia remains unclear, it has been hypothesized that they may underlie some of the decline that occurs during aging. Detection of beta-amyloid in normal individuals offers the opportunity to study the earliest stages of AD, as well as to investigate mechanisms of neural compensation that may preserve normal function. To investigate these hypotheses, we have recruited healthy independently-living elderly subjects from the community to undergo neuropyschological testing, PET imaging, and MRI. The recent development of [11C]PIB ('Pittsburg Compound-B'), a PET radiotracer that binds to beta-amyloid plaques allows the unique opportunity to study the deposition of this pathology in vivo. [unreadable] [unreadable] This measurement of pathology will be compared to cognition in multiple domains, gray matter volume, and glucose metabolism. Furthermore, alterations in brain activation are commonly reported in functional MRI studies of aging, and may reflect neural compensation in response to early amyloid deposition. To understand if beta-amyloid pathology leads to functional compensation, normal subjects studied with PIB will undergo functional magnetic resonance imaging (fMRI) while performing an episodic memory task. PUBLIC HEALTH RELEVANCE: The high prevalence of AD poses a great burden to our society. Since AD pathology is thought to accumulate years before dementia onset, early detection may provide an opportunity to halt further accumulation and prevent conversion to AD. Research that strives to understand the initial stages of this pathology may promote the application of novel anti-amyloid treatments to individuals before dementia onset. [unreadable] [unreadable] [unreadable]